PROJECT SUMMARY Within the general population, women are at increased risk for developing anxiety-related disorders. Many of these mental health disorders are linked to times of hormonal fluctuations (puberty, pre-menstrual disorder, pregnancy, menopause). However, some of these life events (reproductive experience/pregnancy/child rearing) may be beneficial, producing persistent decreases in stress responsiveness that far outlast the post-partum and weaning periods. While much research is focused on mechanisms that cause stress-related disorders, few studies have examined the neural circuits associated with resilience. The long-term goal of this research is to elucidate the brain pathways and mechanisms involved in the establishment and maintenance of stress resilience. While our research team has advanced the understanding of how neuropeptide Y (NPY) works as an anxiolytic compound in the basolateral amygdala (BLA) of male rats, the assessment of stress resilience cannot be complete without identifying the generation of resilience in females. The studies outlined here focus on the role of NPY in establishing stress resilience in females both via injection of the peptide into the amygdala and through endogenous release in a naturally-occurring model of resilience (reproductive experience; RE). We postulate that administration of NPY into the BLA will induce behavioral stress resilience in nave female rats and that this will be accompanied by alterations in BLA neuronal excitability, decreases in ion channel expression and altered BLA neuronal morphology associated with decreased anxiety; a cellular ?signature? that was observed in male rats. To examine whether NPY participates in physiologically-induced resilience, we will use a model of RE (uniparous females rearing one litter), a life experience that increases stress resistance, to assess anxiety-related behaviors and properties of BLA neurons in ex vivo slice preparations. We will also examine gene expression of ion channels and neuropeptide receptors associated with stress resilience, as well as whether blockade of NPY Y5 receptors inhibits the generation of this resilience. The work proposed here will expand the stress resilient role of NPY, and the effects of RE on similar mechanisms (alteration of H currents) to produce stress resilience. While these studies examine mechanisms underlying resilience, the results can also inform future studies of postpartum depression and sex differences in treatment of anxiety disorders. The contribution of the Y5R subtype to the generation of resilience in two different models will be particularly informative in identifying a mechanism and novel target for anxiety treatment.